Synthesis of Organic Halides

Organic halides are important synthetic intermediates in numerous reactions. They are also important due to the variety of radiohalogen-containing pharmaceuticals which have been developed in recent years it has been observed that organo- 

4-Vinylcyclohexene is converted to give the corresponding unsaturated alkyl iodide selectively (Eq. 107) 

This reaction, however, has some obvious disadvantages, 

The reaction is instantaneous with the migration of two alkyl groups to afford the corresponding alkyl iodides (Eq. 108) 

Alkyl bromides can also be obtained from organoboranes by treatment with bromine or bromine chloride 

The stereodefined alkenyl halides are of prime importance due to the recent developments of di- or trisubstituted alkene synthesis by cross-coupling reactions between organometallics and alkenyl halides catalyzed by transition metal compounds 171). These alkenyl halides can be conveniently obtained from alkenylboranes or alkeneboronic acids. B-Alk enylcatecholboranes undergo rapid hydrolysis when stirred with excess water at 25 °C (Eq. 109)102). The alkeneboronic acids are usually crystalline solids of low solubility in water and can be easily isolated and handled in air without significant deterioration. 

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The addition of H—X, where X = F, Cl, Br and I, to alkenes, dienes and alkynes has been extensively studied from both mechanistic1-3 and synthetic standpoints. While it is one of the earliest methods employed for the synthesis of organic halides, it can often lead to mixtures of products, and the direct conversion of the corresponding alcohols is more commonly used nowadays. The early literature abounds with examples of this reaction in which either mixtures of products are formed, or the products are not well characterized. Few major advances have been reported in more recent times which overcome the synthetic disadvantages of this direct process. It can nevertheless be the method of choice for the synthesis of certain substrates. 

Hunsdiecker reaction. Synthesis of organic halides by thermal decarboxylation of silver salts of carboxylic acids in the presence of halogens. 

Coupling of organic halides with carbonyl compounds promoted by Sml2 in synthesis of heterocycles 99CRV745. 

Thomson . Click Organic Interactive to use a web-based palette to design a synthesis of alkyl halides, beginning with alcohols. 

Thayer, John S., Not for Synthesis Only The Reactions of Organic Halides with... 

Another versatile domino process for the synthesis of carbocycles as well as heterocycles is the Pd-catalyzed reaction of organic halides or triflates with alkynes or allenes, which contain a carbo- or heteronucleophile in close vicinity to these functionalities (see Scheme 6/1.75) [133]. 

The dehalogenation of organic halides by organotin hydrides takes place in most cases with a free-radical mechanism [1, 84, 85], The stereospecific reduction of 1,1-dibromo-l-alkenes with Bu3SnH discovered by Uenishi and coworkers [86-89], however, did not occur in the absence of palladium complexes and did not involve radicals. For the synthesis of (Z)-l-bromo-l-alkenes, [(PPh3)4Pd] proved to be the most effective catalyst which could also be generated in situ. The reaction in Eq. (7) proceeded at room temperature and a wide range of solvents could be used. 

Allylation of organic halides. T wo laboratories2 have reported briefly that in the presence of a radical initiator organic halides undergo allylic substitution reactions with allyltrialkyltin compounds in moderate yield. This reaction was used in a recent Synthesis of the neurotoxin (+ )-perhydrohistrionicotoxin (7) to introduce the n-butyl tide chain.3 AI BN-catalyzed reaction of the bromide 2 with 1 proceeds in unexpectedly igh yield and with complete stereocontrol to give a single product 3. It is the tndesired isomer, but the desired stereochemistry is obtained by epimerization of the Intermediate ketone 5. The hydroxy lactam (6) had previously been used for the Synthesis of 7. 

Alkyl halides are important starting materials in the synthesis and manufacture of a variety of organic compounds. Free-radical halogenation (Scheme 4.12) is an important methodology for the synthesis of alkyl halides from alkanes. Brominations (X = Br) tend to be very selective because of the... 

Scheme 5.12 PEG-enhanced synthesis of organic carbamates from amines, C02 and alkyl halides [50]...

An efficient and environmentally benign method for the PEG400-enhanced synthesis of organic carbamates with high chemoselectivity from amines, CO2 and alkyl halides under room temperature and atmospheric pressure utilizing K2CO3 as a base is reported (Scheme 5.12) [50]. PEG probably could serve as both a solvent and PTC, and also activate the carbamic anion so that PEG could depress the alkylation and enhance the selectivity toward the target product. 

It is noteworthy that in 1912 Smith and Kipping678 applied the Barbier synthesis, i.e. the addition of organic halide to a mixture of Mg and SnCU in ether (without preliminary preparation of the Grignard reagent) to obtain organylchlorostannanes in a good yield678,679. 

The reduction of organic halides has been well used for organic synthesis. The rate constants for the reduction of alkyl, aryl, and vinyl radicals are shown in Table 1.10. 

Reduction of organic halides and chalcogenides with Bu3SnH has been used frequently in organic synthesis. Rate constants for the reaction of organic halides and chalcogenides with Bu3Sn are shown in Table 1.13. 

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